The purpose of this mentored training award is to establish the candidate's independent research career examining comorbidity between cigarette smoking and posttraumatic stress disorder (PTSD). The candidate's long-term goal is to identify substrates that underpin nicotine dependence in smokers with PTSD in order to develop tailored treatments that more effectively reduce smoking in this population. These goals will be accomplished through formal didactic coursework, seminars, and practical performance of a laboratory study at the University of Washington and the Veterans Administration Puget Sound Health Care System. Despite strong comorbidity between smoking and PTSD, little is known about mechanisms maintaining smoking in this psychiatric population. Two studies examining affective mechanisms potentially influencing smoking in PTSD are proposed. Study 1 will 1) characterize effects of acute nicotine administration on situationally induced positive affect and situationally induced negative affect, and 2) determine whether nicotine's mood effects are more pronounced among smokers with PTSD versus smokers without PTSD. In counterbalanced order, smokers with PTSD (n = 50) and smokers without PTSD (n = 50) will undergo three positive and three negative laboratory-based mood inductions in combination with: 1) smoking a nicotinized cigarette, 2) smoking a denicotinized cigarette, and 3) drinking water. The magnitude of positive and negative affective responses to the mood inductions will be compared. Study 2 will examine whether the effects of nicotine deprivation on positive affect and negative affect are magnified among smokers with PTSD versus smokers without PTSD. Smokers who participated in Study 1 will stop smoking for 48 hours while being assessed for positive affect, negative affect, and craving via electronic diary. In addition, Study 2 will explore two mechanisms that potentially influence affective response to nicotine deprivation among smokers with PTSD: 1) reliance on nicotine to regulate affect (measured during Study 1) and 2) changes in cortisol after quitting smoking. Salivary cbrtisol will be measured over two days of regular smoking and two days of nicotine deprivation. RELEVANCE: Cigarette smoking is the number one avoidable cause of death and disability. It is estimated that PTSD affects 2.6 million Americans, and that 1.6 million of these patients are smokers.